Amine derivatives having NPY Y5 receptor antagonistic activity and the uses thereof

• US 8,299,265 B2
• Filed: 04/26/2010
• Issued: 10/30/2012
• Est. Priority Date: 10/25/2007
• Status: Expired due to Fees

• Current Assignee: Shionogi & Co., Ltd.
• Original Assignee: Shionogi & Co., Ltd.
• Inventors: Okuno, Takayuki, Sakagami, Masahiro
• Primary Examiner(s): Saeed, Kamal
• Assistant Examiner(s): Grazier, Nyeemah A
• Application Number:
  US12/767,641
• Publication Number:
  US 20100273842A1
• Time in Patent Office: 918 Days
• Field of Search: None
• US Class Current: 548/161
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 2601/04 with a four-membered ring
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2602/08 the other ring being five-membered, e.g. indane
• CPC Class Codes: C07C 2602/10 the other ring being six-membered, e.g. tetraline
• CPC Class Codes: C07C 2603/18 Fluorenes; Hydrogenated fluorenes
• CPC Class Codes: C07C 311/05 to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
• CPC Class Codes: C07C 311/07 having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 311/08 having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 311/21 having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 311/37 having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 311/43 having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 317/36 with the nitrogen atoms of the amino groups bound to hydrogen atoms or to carbon atoms
• CPC Class Codes: C07D 207/14 Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 207/16 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 207/32 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 209/08 : with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 211/26 : with hydrocarbon radicals, substituted by nitrogen atoms
• CPC Class Codes: C07D 211/62 : attached in position 4
• CPC Class Codes: C07D 211/70 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 213/75 : Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 215/38 : Nitrogen atoms nitro radicals C07D215/18
• CPC Class Codes: C07D 217/04 : with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 231/12 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 231/56 : Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C07D 233/68 : Halogen atoms
• CPC Class Codes: C07D 239/42 : One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 257/04 : Five-membered rings
• CPC Class Codes: C07D 265/30 : not condensed with other rings
• CPC Class Codes: C07D 277/42 : Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 277/72 : 2-Mercaptobenzothiazole
• CPC Class Codes: C07D 285/06 : 1,2,3-Thiadiazoles; Hydrogenated 1,2,3-thiadiazoles
• CPC Class Codes: C07D 285/135 : Nitrogen atoms
• CPC Class Codes: C07D 295/135 : with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 307/91 : Dibenzofurans; Hydrogenated dibenzofurans
• CPC Class Codes: C07D 311/16 : substituted in position 7
• CPC Class Codes: C07D 317/48 : Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring

Abstract

This invention provides an anorectic or anti-obesity composition comprising a compound of the formula (I):

• a pharmaceutically acceptable salt or solvate thereof,
• wherein
• R¹ is optionally substituted lower alkyl,
• Y is —S(O)_n— wherein n is 1 or 2, or —CO—,
• R² is hydrogen or lower alkyl,
• R⁷ is hydrogen or lower alkyl,
• X is lower alkylene, lower alkenylene, arylene, cycloalkylene or the like, and
• Z is lower alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl or the like.

Claims

1. A compound selected from the group consisting of:

4. An anorectic or anti-obesity composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 1.

5. A method for suppressing appetite, comprising administering an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

6. A method for treating obesity, comprising administering an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

7. A method for treating an obesity-related disorder, comprising administering an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof wherein said obesity-related disorder is overeating, hypertension, impaired glucose tolerance, diabetes, metabolic syndrome, abnormal lipid metabolism, dyslipidemia, arteriosclerosis, hyperuricemia, gout, fatty liver, endometrial, breast, prostate and colon cancer, osteoarthritis, lumbago, obstructive sleep apnea syndrome, coronary artery disease, cerebral infarction, menstrual disorder, Prader-Willi Syndrome, Frohlich'"'"'s syndrome, or pickwickian syndrome.

8. A method for weight management for obesity, comprising administering an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

9. A method for inducing weight loss, comprising administering an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

10. A method for accelerating weight loss, comprising administering an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

11. A method for maintaining body weight, comprising administering an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

12. A method for managing body weight, comprising administering an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

2. A pharmaceutical composition, comprising a compound selected from the group consisting of:

3. A pharmaceutical composition according to claim 2, exhibiting NPY Y5 receptor antagonistic activity.